A. Calcium Formate as a Phosphate Binder
Phosphorus retention plays a major role in chronic renal failure in the development of both secondary hyperparathyroidism and osteodystrophy. Bricker, N., S. et al., Archives of Internal Medicine 123:543-553 (1969); Rubini, M. E. et al., Archives of Internal Medicine 124:663-669 (1969); Slatopolsky, E., et al., Journal of Clinical Investigation 50:492-499 (1971); Bricker, N. S., New England Journal of Medicine 286:1093-1099 (1972); Slatopolsky, E. S., et al., Kidney Int. 2:147-151 (1972).
Antacids are often used to bind dietary phosphorus to prevent phosphorus retention and prevent its absorption. This process is referred to as phosphorus binding and appears to be a chemical reaction between dietary phosphorus and the cation present in the binder compound, which is usually albumin or calcium. The binding results in the formation of insoluble and unabsorbable phosphate compounds, adsorption of phosphorus ions on the surface of binder particles, or a combination of both.
Presently-used antacids are inefficient at binding phosphorus in vivo. For example, a recent study by Ramirez, et al., noted that even though aluminum-containing or calcium-containing antacids were administered in large excess, they bound only 19-35 percent of dietary phosphorus. Ramirez, J. A., et al., Kidney Int. 30:753-759 (1986). Similar conclusions can be derived from data presented in earlier studies. Kirsner, J. B., Journal of Clinical Investigation, 22:47-52 (1943); Clarkson, E. M., et al., Clinical Science 43:519-531 (1972); Cam, J. M., et al., Clinical Science and Molecular Medicine 51:407-414 (1976); Man, N. K. et al., Proceedings of the European Dialysis and Transplantation Association 12:245-55 (1975).
Antacids are used widely, often in large quantities, for indigestion, heartburn or peptic ulcer disease. Despite their consumption in large amounts and often over long periods of time, phosphorus depletion is uncommon in these settings. This fact is additional evidence of the inefficiency of antacids as phosphorus binding agents.
The inefficiency of commonly used phosphorus binders creates a clinical dilemma. The dose of the binder must be increased to control hyperphosphatemia, but increased risk of toxicity of the binder results from the increased dose. This toxicity includes bone disease and aluminum dementia from aluminum-containing antacids and hypercalcemia and soft tissue calcification from calcium-containing antacids. These risks are particularly problematic in patients with chronic renal disease.
It would be very useful to have a phosphorus binder available which does not have the risks associated with ingestion of presently available binders. The binder should be more efficient in binding phosphorus and, thus, would not have to be consumed in the large quantities necessary, for example, when calcium carbonate-containing compositions are used. Such a phosphorus binder would be particularly valuable for administration to individuals with chronic renal failure, in whom phosphorus retention is a serious concern and the risk of toxicity from consumption of presently-available binders is greater than in individuals in whom kidney function is normal.
U.S. Pat. No. 4,870,105 addresses these concerns by disclosing a calcium acetate phosphorus binder. However, it would be advantageous to find a binder with a smaller anion and, hence, a smaller effective dose.
B. Calcium Formate as a Dietary Supplement
Calcium is an abundant element in the human body and plays an important role in many physiological processes. Nutritional and metabolic deficiencies of calcium can have adverse effects, typically manifested through deficiencies in the structure, function and integrity of the skeletal system. The most common calcium-modulated metabolic bone disorder is osteoporosis.
A preferred approach to calcium supplementation is through dietary sources. Dairy products are the major contributors of dietary calcium, as are green vegetables (e.g. broccoli, kale, turnip greens, Chinese cabbage), calcium-set tofu, some legumes, canned fish, seeds and nuts. Breads and cereals can contribute significantly to calcium intake.
Calcium supplements may be the preferred way to obtain supplemental calcium. Calcium carbonate is usually recommended for economic reasons. However, calcium carbonate usage requires sufficient gastric acids for its utilization. Some individuals, especially the elderly, may have limited amounts of gastric acid, and achlorhydric patients have little gastric acid. For such cases, calcium carbonate is poorly utilized. Using large amounts of calcium carbonate may also lead to constipation and abdominal distention. Calcium lactate or calcium citrate may then be used.
Needed in the art of calcium supplementation is a very soluble calcium supplement with smaller anion and, hence, a smaller effective dose.